The major objective is to study the changes that occur in the hypothalamus, pituitary, gonads and reproductive tract of aging female and male rats, in order to elucidate the mechanisms responsible for loss of reproductive functions. Major emphasis will be placed on studies in female rats that have ceased to exhibit regular estrous cycles, and in males that show a significant decrease in serum testosterone levels. The functional capacity of the hypothalamus will be measured by assaying LHRH, turnover of dopamine, norepinephrine, serotonin and opiate peptides, and ability to respond to stimuli and drugs that normally produce release of gonadotropins in young mature rats. Pituitary release of LH, FSH, PRL, GH and TSH, and gonadal release of steroid hormones will be measured by radioimmunoassay (RIA) in the blood. Attempts will be made to reinitiate estrous cycles and have ceased to cycle, and to induce pregnancies, parturition and lactation in old female rats that have ceased to cycle, and to increase serum testosterone levels in old male rats, principally by use of drugs to stimulate hypothalamic function. Attempts also will be made to prevent reproductive decline, and development of mammary and pituitary tumors in mature rats by continous treatment with L-dopa and/or progesterone for the lifespan of the animals. Gonadotropin receptors in the gonads, and prolactin receptors in the mammary gland, prostate (male rats), liver, kidneys and adrenals, will be measured in old and young rats. The neuroendocrine system of rats and laboratory mice will be compared with that of Peromyscus leucopus (deer mice) which have a lifespan of up to 8 yrs. and a reproductive period of up to 4 1/2 yrs.